Double high-dose chemotherapy with adriamycin, paclitaxel, cyclophosphamide, and thiotepa followed by autologous peripheral blood stem cell transplantation in women with metastatic breast cancer

To determine the feasibility, time to progression, and event-free survival, twenty-two women with metastatic breast cancer received two cycles of high-dose chemotherapy (HDCT) followed by peripheral blood stem cell transplantation (PBSCT) early after first-line induction chemotherapy. The median age of the ten (45.5%) pre- and 12 (54.5%) postmenopausal women was 48 (range: 33-60) years. Sixteen patients (72.7%) had at least two or more metastatic sites involved. Protocol induction and mobilization chemotherapy including granulocyte-colony stimulating-factor (G-CSF) consisted of two cycles with adriamycin (60 mg/m(2)) i.v. and paclitaxel (200 mg/m(2)) i.v. After collection of at least 4 x 10(6)/kg bodyweight peripheral blood stem cells, the first HDCT-course of adriamycin (60 mg/m(2)), paclitaxel (200 mg/m(2)) cyclophosphamide (4 g/m(2)), and thiotepa (800 mg/m(2)) (ATCT) was given to at least stable disease (SD) patients. Six to eight weeks later, the second HDCT-ATCT was administered. Each HDCT-cycle was followed by PBSCT with a median of 3.81 x 10(6)/kg bodyweight CD-34 positive cells (range: 1.85-10.38). All women showed median leukocyte engraftment (>1,000 x 10(9)/l) on day +9.4 (range: 7-13) and median platelet engraftment (>20,000 x 10(9)/l) on day +12.3 (range: 8-15). There were no apparent differences in the clinical course and non-hematologic toxicity between the two HDCT-cycles. Of the 21 patients evaluable for response, eight (38.1%) patients achieved complete remission (CR), ten (47.6%) patients showed a partial remission (PR), two patients (9.5%) no change, and one patient (4.8%) progressive disease. After a median observation time of 36 (range 28-55) months, six (28.6%) women are alive, four (19.0%) of them in continuous CR, including two women with stable bone lesions, respectively, and 15 (71.4%) died due to progressive disease. Median time to progression (TTP) was 8 (range 4-19) months. A high initial response rate of early HDCT, including the most active drugs adriamycin and paclitaxel, can be achieved with tolerable toxicity in metastatic breast cancer. New approaches for maintaining primary tumor response achieved with efficacious high-dose chemotherapy are warranted.